Press Release
Source: Medarex, Inc.
Anti-Cancer Responses in Metastatic Melanoma Patients Linked to Immune
Activation by MDX-010 Published in the `Proceedings of the National Academy
of Sciences' (PNAS)
Wednesday June 25, 6:00 am ET
Complete Responses Observed in On-Going Phase II Clinical Trial
PRINCETON, N.J., June 25 /PRNewswire-FirstCall/ -- Medarex, Inc. (Nasdaq:
MEDX - News) today announced the publication of positive results from the
initial cohort of 14 patients in an open-label MDX-010 Phase II melanoma study
in the Online Early Edition of the "Proceedings of the National Academy of
Sciences" (
www.pnas.org) for the week of June 23, 2003. In the study, an
objective response rate of 21%, which included two complete tumor responses,
was observed in the initial cohort of 14 patients with metastatic melanoma. The
trial was conducted by Steven A. Rosenberg, M.D., Ph.D., Chief of Surgery at
the National Cancer Institute (NCI), and was the first human study designed to
assess the potential anti-tumor activity of MDX- 010, a fully human antibody that
blocks CTLA-4, after repeated dosing in combination with a peptide vaccine
based on gp100 melanoma-associated antigens. Previous studies of this
vaccine given alone without the antibody in the treatment of metastatic
melanoma demonstrated an objective response rate of approximately 2%.
The data also indicates that
MDX-010 may be able to induce
a reversible state of
autoimmunity, with an apparent
correlation between the
development of drug-related
autoimmunity and durable clinical
responses. Six patients reported
drug-related autoimmune adverse
events (dermatitis, colitis,
hepatitis and hypophysitis), all of
whom responded to medical
therapy. Of the patients who
experienced these Autoimmune
Breakthrough Events (ABEs),
50% also experienced anti-tumor
response. No patient experienced an anti-tumor response without experiencing
some ABE. The observations suggest that these drug- related adverse events,
or Autoimmune Breakthrough Events, may be associated with the induction of
anti-cancer immune responses.
In the initial cohort of 14 patients with metastatic disease, all had undergone
surgical therapy for the primary lesion and received a regimen of 3.0 mg/kg of
MDX-010 once every three weeks in combination with two peptides from the
gp100 melanoma-associated antigen, gp100:209-217(210M) and gp100:280-
288(288V). Of these, two patients achieved complete responses, per the
RECIST (Response Evaluation Criteria in Solid Tumors) definition. One of these
two patients experienced complete resolution of a 0.5 cm brain lesion, two
subcutaneous nodules and 31 lung metastases. The second of these two
patients experienced complete resolution of an abdominal subcutaneous nodule
and a solitary lung lesion. Prior to treatment with the MDX-010 antibody and
gp100 peptide vaccine, both patients had received chemotherapy and
undergone surgical therapy, and one patient had also received previous
immunotherapy. A third patient who had received previous immunotherapy
achieved a partial response with tumor shrinkage of a solitary lung lesion,
lasting over 10 months after two treatment cycles. Mixed responses were
observed in two additional patients.
These results were recently presented at the 2003 annual meeting of the
American Society of Clinical Oncology (ASCO 2003 Abstract
#3424). The
ongoing Phase II trial is expected to enroll up to 55 patients.
"We are excited by these significant anti-tumor responses in metastatic disease
and by the apparent correlation of tumor responses with the advent of
Autoimmune Breakthrough Events," said Geoffrey M. Nichol, M.D., Senior Vice
President of Product Development at Medarex. "We believe that these
preliminary results demonstrate the potential of MDX-010 to break tolerance to
self in a predictable and reversible fashion and that during this temporary
autoimmune state, useful anti-tumor effects can be seen. The ABEs themselves
are markedly less troublesome than the adverse event profiles observed in the
current forms of standard melanoma treatment."
"We believe that MDX-010 has the potential to become a significant treatment
for melanoma and other serious diseases," said Donald L. Drakeman,
President and CEO of Medarex. "We are greatly encouraged that some
patients with metastatic disease still appear cancer-free, and we look forward to
additional data later in the year that may further demonstrate the benefits of
MDX-010 in patients."
MDX-010 is currently in multiple Phase II clinical trials to test the product for use
in patients with melanoma and prostate cancer. MDX-010 is also being tested
in a Phase I clinical trial for HIV.
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